This proposal will specifically foster the development of the candidate, Lino Becerra Ph.D., in Biomedical Research. Dr. Becerra has a strong background in physics and magnetic resonance imaging and will apply knowledge to functional imaging of pain. Through this proposal, he seeks to gain the following: 1) An in-depth knowledge of the neurobiology of pain, including brain mechanisms involved in nociception and hyperalgesia, 2) training in the implementation of experimental paradigms in human experiments, and 3) experience applying quantitative methods for analysis of fMRI data. This proposal utilizes quantitative temporal analysis to examine ventral nervous system (CNS) activation in reward circuitry (sublenticular extended amygdala, amygdala, nucleus accumbens, orbitofrontal cortex and ventral tegmentum) versus pain circuitry (somatosensory cortex, anterior cingulate, thalamas, insula) in two models of pain. These models are experimental noxious heat as a model of nociception, and heat with topical capsaicin as a model of hyperalgesia. Our recent neuroimaging studies had revealed activation in reward/aversion circuitry that is distinct from the activation of classic somatosensory systems reported in the pain neuroimaging literature. Using new analytical methods developed by the candidate to assess the temporal nature of the hemodynamic response we will quantify the activation in pain circuitry compared with reward circuitry. We will test the following hypotheses: a) that the multiphasic hemodynamic response to nociceptive (thermal) pain activates differentially reward and pain circuitry, and b) that non-noxious thermal and mechanical stimuli will activate reward and pain circuitry in models of primary and secondary hyperalgesia. The research will be integrated with coursework, literature review, attendance at scientific meeting, and interactions with and instruction from established pain scientists in animal and human studies in a manner that will advance Dr. Becerra's development as a productive, independent investigator. He is committed to study of brain mechanisms underlying somatosensory and emotional brain circuitry and how they contribute to the experience of pain under experimental and clinical conditions in human subjects.